10-16695157-TG-T

Position:

• chr10-16695157-TG-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6 BS2

The ENST00000345264.10(RSU1):​c.599-3del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0086 in 1,171,714 control chromosomes in the GnomAD database, including 4 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00020 (0 hom., cov: 17)
  • Exomes 𝑓: 0.0096 (4 hom.)
• Consequence: RSU1 ENST00000345264.10 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Likely benign no assertion criteria provided B:2
• Conservation: PhyloP100: 2.33

Genes affected

RSU1 (HGNC:10464): (Ras suppressor protein 1) This gene encodes a protein that is involved in the Ras signal transduction pathway, growth inhibition, and nerve-growth factor induced differentiation processes, as determined in mouse and human cell line studies. In mouse, the encoded protein was initially isolated based on its ability to inhibit v-Ras transformation. Multiple alternatively spliced transcript variants for this gene have been reported; one of these variants was found only in glioma tumors. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• BP6: Variant 10-16695157-TG-T is Benign according to our data. Variant chr10-16695157-TG-T is described in ClinVar as [Likely_benign]. Clinvar id is 1328202.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RSU1	NM_012425.4	c.599-3del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000345264.10	NP_036557.1
RSU1	NM_152724.3	c.440-3del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			NP_689937.2
RSU1	XM_047425617.1	c.598+57381del		intron_variant			XP_047281573.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RSU1	ENST00000345264.10	c.599-3del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_012425.4	ENSP00000339521	P1

Frequencies

GnomAD3 genomes AF: 0.000195 AC: 25 AN: 128178 Hom.: 0 Cov.: 17

Gnomad AFR AF: 0.000232

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000154

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000281

Gnomad FIN AF: 0.000293

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000183

Gnomad OTH AF: 0.000578

GnomAD4 exome AF: 0.00964 AC: 10055 AN: 1043536 Hom.: 4 Cov.: 21 AF XY: 0.00977 AC XY: 5064 AN XY: 518274

Gnomad4 AFR exome AF: 0.00281

Gnomad4 AMR exome AF: 0.0148

Gnomad4 ASJ exome AF: 0.0118

Gnomad4 EAS exome AF: 0.00519

Gnomad4 SAS exome AF: 0.00902

Gnomad4 FIN exome AF: 0.0137

Gnomad4 NFE exome AF: 0.00958

Gnomad4 OTH exome AF: 0.0109

GnomAD4 genome AF: 0.000195 AC: 25 AN: 128178 Hom.: 0 Cov.: 17 AF XY: 0.000213 AC XY: 13 AN XY: 61060

Gnomad4 AFR AF: 0.000232

Gnomad4 AMR AF: 0.000154

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000281

Gnomad4 FIN AF: 0.000293

Gnomad4 NFE AF: 0.000183

Gnomad4 OTH AF: 0.000578

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: no assertion criteria provided

Submissions by phenotype

not provided Benign:2

Likely benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs56715139; hg19: chr10-16737156;